A major example of non-invasive method for diagnosing arteriosclerosis includes X-ray angiography. This method contrasts vascular flows by using a water-soluble iodine-containing contrast medium, and therefore, the method has a problem of difficulty in distinguishing pathological lesions from normal tissues. By applying the above method, only a pathological lesion where constriction progresses 50% or more can be detected, and it is difficult to detect a lesion before onset of attack of an ischemic disease.
As diagnostic methods other than the above, methods of detecting a disease by nuclear magnetic resonance tomography (MRI) using a contrast medium, which is kinetically much distributed in arteriosclerotic plaques, have been reported in recent years. However, all the compounds reported as the contrast medium have a problem for use in the diagnostic methods. For example, hematoporphyrin derivatives (see, U.S. Pat. No. 4,577,636, the disclosure of which is expressly incorporated by reference herein in its entirety) are pointed out to have a defect of, for example, dermal deposition and coloring of skin. As for gadolinium complexes having a perfluorinated side chain, which have been reported to accumulate in lipid-rich plaques (see, Circulation, 109, 2890, 2004, the disclosure of which is expressly incorporated by reference herein in its entirety), accumulation in lipid-rich tissues and organs in vivo, such as fatty livers, renal epitheliums, and tendons of muscular tissues is of concern.
From a viewpoint of chemical compounds, compounds having two fatty acid ester moieties are known in which phosphatidylethanolamine (PE) and diethylenetriaminepentaacetic acid (DTPA) are bound via an amide bond (for example, Polymeric Materials Science and Engineering, 89, 148 (2003), the disclosure of which is expressly incorporated by reference herein in its entirety), and liposomes using gadolinium complexes of such compounds are also reported (Inorganica Chimica Acta, 331, 151 (2002), the disclosure of which is expressly incorporated by reference herein in its entirety). However, since these complexes are hardly soluble, they have poor property of handling in liposome formation. Accumulation and toxicity of these complexes in vivo are also of concern.
Separately reported gadolinium complexes introduced with one higher fatty acid ester group as a hydrophobic group (see, Japanese Unexamined Patent Publication (KOKAI) No. 2007-91640, the disclosure of which is expressly incorporated by reference herein in its entirety) have favorable solubility, and can also be used for liposome preparation. However, the complexes have a problem that the amount thereof to be incorporated into liposomes is limited to a low concentration. This is presumably because the complexes disclosed in the aforementioned publication are so-called wedge shape molecules, and therefore their compatibility with liposomes constituted by cylinder shape molecules is low.